This project involves the biological and molecular characterization of murine leukemia viruses (MuLV) with the aim of understanding host and viral factors involved in the pathogenesis of neoplastic and non-neoplastic sequelae of infection. 1) Induction of the murine lymphoproliferative and immunodeficiency disease mouse AIDS (MAIDS) is accomplished by infection of mice of sensitive strains by the LP-BM5 complex of viruses consisting of an etiologic defective virus (BM5def) and B-tropic ecotropic and mink cell focus-inducing (MCF) helper MuLVs, or by the molecularly clone BM5def pseudo typed by an appropriate helper virus. The presence of replication competent virus greatly enhances disease induction although MAIDS can be initiated in its absence using stocks of virus prepared in a packaging cell line. Expression of the defective virus is essential but not solely sufficient for disease induction. Genes of the MHC complex are major regulators of sensitivity and resistance in laboratory mice and in attempts to understand the mechanisms of immune resistance, early studies implicated CD8+ T cells. To examine further this aspect of control of virus infection and disease, we tested mice lacking CD8+ T cells due to disruption of the gene for beta microglobulin (beta2M) or deficient in perforin as a result of knock-out of the perforin gene. Mice of a MAIDS-resistant strain when homozygous for the beta2M knock-out developed early lymphoproliferation and immune system defects but proliferation did not progress to levels found in mice of MAIDS-sensitive strains. Similarly, mice homozygous for the perforin defect were more sensitive than wild-type mice but with a non-progressive disease phenotype. Thus perforin-dependent CD8+ T cell mediated control plays a role in MAIDS resistance but other mechanisms also contribute. 2) In one aspect of studies of the mechanism of B lineage lymphomagenesis in NFS mice congenic for ecotropic MuLV-inducing loci, a virus preparation obtained from a spontaneously occurring B cell lymphoma has induced a B cell lymphoblastic lymphoma in mice inoculated as newborns. A high titer of MCF virus is associated with the initial tumor and occurs in recipient mice and studies are in progress to characterize the virus(es) involved and their pathogenecity.